Hypogammaglobulinaemia after rituximab treatment—incidence and outcomes

[Joolz]

Very difficult to weigh up the risks and benefits there. I guess it would be inappropriate as part of the current trial

Didn't they give IVIG to some of the RTX patients in the third (?) study when their IgG levels dropped? Or where do I get that idea from?

and beyond that things are rather hypothetical.

Well, it could be quite an interesting question to discuss for the Kogelnik patients.

 

[Joolz]

Sub cut is fine but you need to be reasonably well trained to do it without going in the wrong place.

Oh, really? I thought you just put the needle right under your skin on your upper arm or leg or in your stomach fat and make sure you didn't hit any blood vessel? Is there more to it than that?

 

[Jonathan Edwards]

Oh, really? I thought you just put the needle right under your skin on your upper arm or leg or in your stomach fat and make sure you didn't hit any blood vessel? Is there more to it than that?

Not much, but people get local reactions and may need to move from place to place and there are safe places to use and not so safe places where there are major vessels or nerves or just places where the stuff won't go in.

 

[deleder2k]

Didn't they give IVIG to some of the RTX patients in the third (?) study when their IgG levels dropped? Or where do I get that idea from?
Well, it could be quite an interesting question to discuss for the Kogelnik patients.

Two patients in the blinded trial were treated with Kiovig IVIG infusions after recurrent upper respiratory infections. They also got AB.

 

[Marky90]

What would you say is the recommended dosage @Jonathan Edwards? In this study (http://www.researchgate.net/publica...apy_in_patients_with_chronic_fatigue_syndrome) where IVIG apparantly had a significicant effect. its 2g per kg? Or am i misunderstanding something here? If thats right its much higher than people in Norway is taking.

 

[Jonathan Edwards]

What would you say is the recommended dosage @Jonathan Edwards? In this study (http://www.researchgate.net/publica...apy_in_patients_with_chronic_fatigue_syndrome) where IVIG apparantly had a significicant effect. its 2g per kg? Or am i misunderstanding something here? If thats right its much higher than people in Norway is taking.

That was a study of high dose IVIG as an immunomodulator, which is quite different from replacement. The replacement dose is whatever is needed to get the levels up to something near normal.

 

[Marky90]

That was a study of high dose IVIG as an immunomodulator, which is quite different from replacement. The replacement dose is whatever is needed to get the levels up to something near normal.

Right! I just talked to a girl who got her life back when given high dose IVIG, which together with the above study gets me thinking that there might be something to it..

 

[deleder2k]

How is the uptake of immunoglobulins with IM injection versus IV? I've heard Mella mentioning that a patient quickly responded to a Kiovig IV infusion. When I speak to patients that has benefitted from IM gammaglobulin they all say that it took at least 4-6 weeks before things started to happen.

Is such a major difference plausible? Could one benefit from IV weeks, or even months before IM?

I guess it also could be to the different in doses. Recommended start dose is often 28-56 grams of IgG with IV for primary immunodeficiency. Those I spoke to who got it IM received 5 ml with Gammanorm (165mg/ml). That equals under 1 gram given weekly.

 

[Nielk]

I was given one dose and then another two weeks later of Rituximab for my RA over a year ago, My IG levels have been steadily dropping since then. I get it checked about every 3 months. Before Rituximab my IGG level was 864 now it is 610. My IGM was 37 (which is already low) now it is 11! I have not had any Rituximab doses since a year ago. In the past 6 months, I had two sinus infections and one case of bronchitis.
@Jonathan Edwards - Is it normal for my numbers to keep dropping like this?

 

[Jonathan Edwards]

I was given one dose and then another two weeks later of Rituximab for my RA over a year ago, My IG levels have been steadily dropping since then. I get it checked about every 3 months. Before Rituximab my IGG level was 864 now it is 610. My IGM was 37 (which is already low) now it is 11! I have not had any Rituximab doses since a year ago. In the past 6 months, I had two sinus infections and one case of bronchitis.
@Jonathan Edwards - Is it normal for my numbers to keep dropping like this?

That sort of fall would be quite common. IgM quite often falls more but both come back to normal once B cells are re-established. The key question is what has happened to your CD19 B cell count. Once that is back to normal IgG and IgM should go back to what they were before. 610 is just below the reference range for IgG but not a problem and as far as we know IgM drops are not a problem. The sinus and bronchial infections are unlikely to be related to low IgG. Recovery from respiratory infections is mostly from innate mechanisms and established immunity since the bacteria involved are likely to be ones you have met many times before.

 

[Nielk]

That sort of fall would be quite common. IgM quite often falls more but both come back to normal once B cells are re-established. The key question is what has happened to your CD19 B cell count. Once that is back to normal IgG and IgM should go back to what they were before. 610 is just below the reference range for IgG but not a problem and as far as we know IgM drops are not a problem. The sinus and bronchial infections are unlikely to be related to low IgG. Recovery from respiratory infections is mostly from innate mechanisms and established immunity since the bacteria involved are likely to be ones you have met many times before.

Thank you for your reply. My latest labworkers shows CD 19 at less than 1. I guess my body is very slow at replenishing my B cells.

 

[Jonathan Edwards]

Thank you for your reply. My latest labworkers shows CD 19 at less than 1. I guess my body is very slow at replenishing my B cells.

Slowish but not unusual. B cells can stay away for a year, or even sometimes two to four years. But most of the drop in Ig is in the first 6 months probably because that is the wash out of the short lived spleen plasma cells. If you were on treatment in our unit everyone would be quite happy with the bloodwork. The great pity is that you have not had the benefit in symptoms. It might still happen but I cannot pretend it is very likely at this stage.

 

[deleder2k]

I hear reports from Haukeland that someone classified as a minor responded after 80 weeks(!). The effect wasn't something to brag about though, but it was said that RTX was the likely factor behind the benefit in symptoms.

From what I understand it seems that patients that benefit the most experience the effect more rapidly than moderate and minor responders.

 

[Marky90]

I was just wondering, @Jonathan Edwards , if you could explain how long the different b-cells live? Im aware this depends on various factors like antigen presentation etc..

 

[Jonathan Edwards]

I was just wondering, @Jonathan Edwards , if you could explain how long the different b-cells live? Im aware this depends on various factors like antigen presentation etc..

That is a very complicated question and the answers are not fully known. Most B cells probably die within days through lack of antigen to meet up with. Memory B cells may last for years in follicles but it is not clear exactly how long. Successful B cells turn into more B cells, which may undergo further mutation, and into plasma cells, which may live for at least ten years.

 

[msf]

Prof. Edwards, earlier in the thread you said that the reason that IVIG is used is not to replenish IgG levels, but to replace the patient's IgG with a healthy person's IgG. I don't fully understand what you mean by this. IVIG was used in those Ritux patients with Hypogammaglobulinaemia - this would seem to be replenishing, since the aim is to get the patient's IgG levels to where they were before they were treated.

I also find it difficult to understand how diminished IgM and IgA levels are not important. I can sort of see why IgM might not be important, if the body is still able to produce IgM in response to a new infection (the question then is whether the B-cell depletion would significantly reduce this), but surely IgA is important, since this is the major immunoglobulin in the gut, and diminished levels would have an immediate impact on the immune system's regulation of the gut, wouldn't they?

 

[msf]

Oh, and I found this paper to be quite informative re: the incidence of side effects of Ritux in RA patients: http://www.medscape.com/viewarticle/771063

 

[Marky90]

Prof. Edwards, earlier in the thread you said that the reason that IVIG is used is not to replenish IgG levels, but to replace the patient's IgG with a healthy person's IgG. I don't fully understand what you mean by this. IVIG was used in those Ritux patients with Hypogammaglobulinaemia - this would seem to be replenishing, since the aim is to get the patient's IgG levels to where they were before they were treated.

Msf, I think the theory is that IVIG reduces the amount of own antibodies, by some mechanism that is not yet understood. Maybe by competition for the Fc-receptors, which would reduce self-antibodies`s half-life. If ME is a variant of a autoimmune disease, it makes sense that this process makes us better. However this doesnt mean that IVIG could not also be used to replenish IgG levels, taken together with Rituximab. I believe, however, that Jonathan has stated earlier that the latter isnt necessary in the short run.

Is that about right @Jonathan Edwards ?

 

[Marky90]

Oh, and I found this paper to be quite informative re: the incidence of side effects of Ritux in RA patients: http://www.medscape.com/viewarticle/771063

Are you able to upload it here?

 

[msf]

It's open access.